Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

Drug Design, Development and Therapy
Debin YuZhihua Zou

Abstract

Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the exp...Continue Reading

Citations

Oct 4, 2019·Journal of Cellular and Molecular Medicine·Jia-Min WangLin-Chong Su
Mar 4, 2017·Journal of Immunology Research·Janina BrueningGisa Gerold
Nov 27, 2020·Frontiers in Veterinary Science·Nancy Patricia CardosoAlejandra Victoria Capozzo

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
ion-exchange chromatography
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism
- Pad

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.